Nutrition and Obesity Group, Department of Nutrition and Food Science, Faculty of Pharmacy, University of Basque Country (UPV/EHU) and Lucio Lascaray Research Centre, 01006 Vitoria, Spain.
Bioaraba Health Research Institute, 01009 Vitoria, Spain.
Int J Mol Sci. 2021 Jan 30;22(3):1384. doi: 10.3390/ijms22031384.
Phenolic compounds have emerged in recent years as an option to face insulin resistance and diabetes. The central aim of this study was: (1) to demonstrate that physiological doses of resveratrol (RSV) or quercetin (Q) can influence glucose metabolism in human myotubes, (2) to establish whether AMP-activated protein kinase (AMPK) and protein kinase B -PKB- (Akt) pathways are involved in this effect. In addition, the effects of these polyphenols on mitochondrial biogenesis and fatty acid oxidation were analysed. Myotubes from healthy donors were cultured for 24 h with either 0.1 μM of RSV or with 10 μM of Q. Glucose metabolism, such as glycogen synthesis, glucose oxidation, and lactate production, were measured with D[U-C]glucose. β-oxidation using [1-C]palmitate as well as the expression of key metabolic genes and proteins by Real Time PCR and Western blot were also assessed. Although RSV and Q increased pgc1α expression, they did not significantly change either glucose oxidation or β-oxidation. Q increased AMPK, insulin receptor substrate 1 (IRS-1), and AS160 phosphorylation in basal conditions and glycogen synthase kinase 3 (GSK3β) in insulin-stimulated conditions. RSV tended to increase the phosphorylation rates of AMPK and GSK3β. Both of the polyphenols increased insulin-stimulated glycogen synthesis and reduced lactate production in human myotubes. Thus, physiological doses of RSV or Q may exhibit anti-diabetic actions in human myotubes.
近年来,酚类化合物已成为应对胰岛素抵抗和糖尿病的一种选择。本研究的主要目的是:(1)证明生理剂量的白藜芦醇(RSV)或槲皮素(Q)可影响人肌管中的葡萄糖代谢;(2)确定 AMP 激活的蛋白激酶(AMPK)和蛋白激酶 B-PKB-(Akt)途径是否参与这种作用。此外,还分析了这些多酚对线粒体生物发生和脂肪酸氧化的影响。将来自健康供体的肌管在 0.1 μM RSV 或 10 μM Q 中培养 24 小时。用 D[U-C]葡萄糖测量葡萄糖代谢,如糖原合成、葡萄糖氧化和乳酸产生。还使用 [1-C]棕榈酸评估 β-氧化以及通过实时 PCR 和 Western blot 评估关键代谢基因和蛋白质的表达。尽管 RSV 和 Q 增加了 pgc1α 的表达,但它们并没有显著改变葡萄糖氧化或 β-氧化。Q 在基础条件下增加了 AMPK、胰岛素受体底物 1(IRS-1)和 AS160 的磷酸化,在胰岛素刺激条件下增加了糖原合酶激酶 3(GSK3β)的磷酸化。RSV 倾向于增加 AMPK 和 GSK3β 的磷酸化速率。这两种多酚均增加了胰岛素刺激的人肌管中的糖原合成并减少了乳酸的产生。因此,生理剂量的 RSV 或 Q 可能在人肌管中表现出抗糖尿病作用。